A study on the treatment protocol of the NHL-BFM and NOPHO Studien GruppenT for mature B-cell non-Hodgkin lymphoma and Burkitt leukemia in children and adolescents (B-NHL 2013)

Aggressive B-cell non-Hodgkin lymphomas (B-NHL) and Burkitt leukemia (B-AL) are aggressive cancers that arise from the B cells of the immune system. B cells are a type of lymphocyte, a kind of white blood cell, and are normally responsible for defending the body against pathogens. These diseases primarily affect the lymphatic system and usually lead to enlarged lymph nodes and B-symptoms such as fatigue and fever. Aggressive non-Hodgkin lymphomas include, among others, Burkitt lymphoma—which encompasses Burkitt leukemia—and diffuse large B-cell lymphoma (DLBCL).

These aggressive types of lymphoma are usually treated with intensive combination chemotherapy; the choice of medications depends on the stage of the disease. The study drug, rituximab, is an antibody that specifically binds to a surface protein (CD20) on B cells and triggers their destruction by the immune system. Rituximab has long been an established component of B-cell lymphoma therapy and is therefore approved. The B-NHL 2013 study investigates the role of rituximab in various stages of aggressive mature B-cell NHL to determine whether, in certain stages, less intensive chemotherapy could be used with the help of the well-tolerated antibody rituximab. There are a total of 5 study arms with varying disease severity; assignment between study arms 2 and 3, and 4 and 5, is random and open-label, meaning that all participants are aware of their assignment. For all groups, the primary outcome being monitored is event-free survival (EFS); an “event” refers, for example, to disease progression. To this end, participants will be examined regularly for up to 7 years after the start of the study. In cases of very limited disease (R1/R2, Stages I and II), the study examines whether replacing anthracyclines with rituximab alters event-free survival (EFS) rates. To this end, one study group receives the standard chemotherapy regimen described here (cyclophosphamide, cytarabine, dexamethasone, etoposide, ifosfamide, methotrexate, prednisolone, vincristine) and, instead of the anthracyclines normally used, a dose of rituximab 5 days before the start of chemotherapy. In cases of limited disease (R2 Stage III), the study investigates whether adding rituximab to standard chemotherapy improves EFS. There are two study arms: one (Study Arm 2) receives standard chemotherapy (as described above + doxorubicin hydrochloride + vindesine sulfate), and the other (Study Arm 3) additionally receives a dose of rituximab 5 days before the start of treatment. For advanced disease (R3/R4), the study compares efficacy in patients who receive either a single dose (Study Arm 4: 5 days before the start of therapy) or seven doses of rituximab (Study Arm 5) in addition to standard chemotherapy (see above).

All individuals under the age of 18 who have a new diagnosis of aggressive mature B-cell NHL or B-AL are eligible to participate. The cancer must be confirmed by histological, cytological, and immunological tests and must not have been treated previously.